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Actinobacillus actinomycetemcomitans is present in elevated proportions and numbers in dental bacterial biofilms of patients with localized aggressive periodontitis. This variant of periodontal disease, occurring in adolescents and young adults, is characterized by rapid and severe destruction of the connective tissues and bone supporting the teeth, eventually culminating in tooth loss. The cytolethal distending toxin (Cdt) is a newly discovered bacterial protein toxin, uniquely present in A. actinomycetemcomitans among all known to-date oral bacterial species. The Cdt has the capacity to inhibit mammalian cell growth, but its putative role in the pathogenesis of the disease is unclear. The aim of this in vitro work has been to study the effects of A. actinomycetemcomitans on periodontal connective tissue cell cultures, and to evaluate the possible involvement of its Cdt. A. actinomycetemcomitans inhibited the proliferation of gingival and periodontal ligament fibroblasts, as a result of a combined arrest at the G1 and G2/M phases of the cell cycle. This growth inhibition was non-lethal and the cells remained metabolically active, although their DNA synthesis was reduced. The intoxicated cells exhibited increased size and irregular structure, characterized by distension and elongation. This cellular enlargement occurred in both G1 and G2/M phase arrested cells. The Cdt of A. actinomycetemcomitans was responsible for the observed growth inhibition, as well as the concomitant morphological alterations. The possible induction of inflammatory cytokines related to bone resorption was investigated in response to A. actinomycetemcomitans, and the involvement of Cdt was evaluated. Extensive focus was given to the study of receptor activator of NF-κB ligand (RANKL) expression, a membrane-bound ligand that signals osteoclast progenitors to differentiate and fuse into mature osteoclasts, activating bone resorption. It was demonstrated that A. actinomycetemcomitans induced RANKL mRNA and protein expression in the cells studied, but did not affect the expression of its decoy receptor, osteoprotegerin. This induction was solely attributed to its Cdt, as demonstrated by the use of a cdt-knockout A. actinomycetemcomitans strain, purified recombinant Cdt, and antibodies blocking the Cdt. In addition, this event was not mediated by pro-inflammatory cytokines known to stimulate RANKL. Interleukin-6 mRNA and protein expression were also enhanced by A. actinomycetemcomitans, but Cdt had limited involvement in this enhancement. In conclusion, two distinct mechanisms by which A. actinomycetemcomitans Cdt may be involved in the pathogenesis of localized aggressive periodontitis are proposed. Firstly, the growth arrest of the resident fibroblasts may impair the physiological connective tissue remodelling equilibrium and lead to connective tissue attachment loss. Secondly, the induction of RANKL by these cells, residing in the proximity of the alveolar bone, may locally stimulate osteoclastogenesis and promote alveolar bone resorption. This work also provides further insights to the understanding of Cdt mechanisms of action, contributing to the global characterization of the toxin’s virulence.

The purpose of this prospective, randomized, controlled clinical investigation is to evaluate the performance of the Motorized Ridge Expanders (MRE), and to compare its results with the ones achieved utilizing lateral ridge augmentation (LRA). Eight subjects with bilateral ridge deformities were selected. One technique was used on the right site and the other on the left site. Implants were placed six months after the bone augmentation procedures. All the measurements were recorded at 2 and 5 mm from the most coronal part of the crest. The augmentation achieved with both techniques was statistically significant, 1.2 mm in the LRA, 1.5 mm in MRE at 2 mm from the crest; 1.5 mm and 1.6 mm respectively at 5mm from the crest. The differences between the two techniques were statistically insignificant. The amount of expansion achieved in the MRE site appears to be negatively correlated (P-Value <0.05) with the thickness of the cancellous bone, and it is not affected by the thickness of the cortical plate. The MRE technique appears to be as effective as the LRA technique in augmenting the thickness of atrophic ridges. The defect treated with the MRE showed less bone width contraction during the first 6 months of healing. Histologically, the regenerated bone was vital, trabecular in nature and in direct contact with bone graft particles. / El propósito de esta investigación clínica prospectiva y aleatoria es comparar el aumento horizontal de la cresta alveolar obtenido con el uso de los expansores motorizados de cresta (EMC) y con regeneración ósea guiada (ROG). Fueron selecccionados ocho pacientes con deformidades horizontales del reborde alveolar bilaterales que iban a recibir implantes dentales. Una técnica de regeneración se utilizó en el lado derecho y la otra en el lado izquierdo, para un total de 23 muestras, 13 en el lado experimental (EMC) y 10 en el lado control (ROG). Los implantes fueron colocados seis meses después de los procedimientos de aumento óseo, y se obtuvo una muestra de hueso para estudio histológico. Todas las mediciones clínicas se registraron a los 2 y 5 mm de la parte más coronal de la cresta. El aumento logrado con ambas técnicas fue estadísticamente significativo, de 1,2 mm en la ROG y 1,5 mm con los EMC a 2 mm de la cresta; y 1,5 mm y 1,6 mm, respectivamente, a 5mm de la cresta. Las diferencias entre las dos técnicas no fueron estadísticamente significativas. La cantidad de expansión lograda en el sitio de los EMC parece tener una correlación negativa (p <0,05) con el grosor del hueso esponjoso, y no se ve afectada por el grosor de la cortical. Histológicamente se observó osteoconductividad del injerto óseo y más partículas residuales del mismo en el lado experimental. La técnica de los EMC parece ser tan eficaz como la técnica de ROG en el aumento de la anchura de las crestas atróficas. Los defectos tratados con los EMC mostraron una menor contracción del injerto óseo durante los 6 meses de cicatrización. / El propòsit d'aquesta recerca clínica prospectiva i aleatòria és comparar l'augment horitzontal de la cresta alveolar obtingut amb l'ús dels expansors motoritzats de cresta (EMC) i amb regeneració òssiaguiada (ROG). Es van selecccionar vuit pacients amb deformitats horitzontals bilaterals de la cresta alveolar on es col.locaren implants dentals. Una tècnica de regeneració es va emprar en el costat dret i l'altra a la banda esquerra, per a un total de 23 mostres, 13 al costat experimental (EMC) i 10 en el costat control (ROG). Els implants van ser col.locats sis mesos després dels procediments d'augment ossi, i es va obtenir una mostra d'os per estudi histològic.Totes les mesures clíniques es van registrar als 2 i 5 mm de la part més coronal de la cresta. L'augment aconseguit amb ambdues tècniques va ser estadísticament significatiu, de 1,2 mm a la ROG i 1,5 mm amb els EMC a 2 mm de la carena, i 1,5 mm i 1,6 mm, respectivament, a 5mm de la cresta. Les diferències entre les duestècniques no van ser estadísticament significatives. La quantitat d'expansió aconseguida en el lloc dels EMC sembla tenir una correlació negativa (p<0,05) amb el gruix de l'os esponjós, i no es veu afectada per el gruix de la cortical. Histològicament es observar osteoconductividad l'empelt ossi i més partícules residuals d'aquest en el costat experimental. La tècnica dels EMC sembla ser tan eficaç com la tècnica de ROG en l'augment de l'amplada de les crestes atròfiques. Els defectes tractats amb els EMC mostrar una menor contracció de l'empelt ossi durant els 6 mesos de cicatrització.

In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

Made available in DSpace on 2014-07-29T15:21:58Z (GMT). No. of bitstreams: 1 Dissertacao parte1 Larissa Santana Arantes Elias.pdf: 1237563 bytes, checksum: 572e0535bd8ddf8a3d9cd5c693a6aa5f (MD5) Previous issue date: 2010-03-19 / The RANK (receptor activator of nuclear factor Kappa-Beta)-RANKL (receptor activator of nuclear factor-kappa beta ligand)-OPG (osteoprotegerin) system is the principal means of differentiating and activating osteoclasts. Changes along this path have been associated with various bone related lesions (BRL), whether benign or malignant, such as osteosarcoma (OS). This system induces resorption when it is deregulated, and in the case of LROs, by replacing the bone tissue for fibrous tissue with the presence of various forms of ossification. And in this same context another protein, osteocalcin (OC), a marker of late ossification, plays a key role in the diagnosis of these lesions. This being so, the objective of this study was to identify, quantify and compare cell RANK+, RANKL+, OPG+ and OC+ in lesions of the jaw with bone involvement: ossifying fibroma (OF), fibrous dysplasia (FD), simple bone cysts (SBC), central giant cell lesions (CGCL) and osteosarcoma (OS) so as to contribute to understanding the pathogenesis and establishing the diagnosis of these lesions. RANK+, RANKL+, OPG+ and OC+ cells were identified by the technique of immunohistochemistry, a method of immunoperoxidase and polymer, in 10 samples of OF, FD, SBC, CGCL and 5 samples of OS. Our results showed that all samples were positive for RANK, RANKL, OPG and OC. In the stromal fibroblast-like cells, the OF (P<0.001), CGCL (P=0.007) and OS (P=0,058) presented a greater expression of RANKL than OPG, in contrast with both the SBC (P=0.003) and the FD (P<0.001). As for bone-matrix (cells around bone/osteoid-osteoblast and osteoclast), the OS (P=0.24) and OF (P=0.001) samples demonstrated a higher RANKL immunoreactivity and and a lower in FD (P=0.001) and SBC (P=0.4) samples. In terms of OC, a higher expression was shown in FD, SBC, and OS (P=0.008). Our results suggest that OF, CGCL and OS express bone metabolism regulators, which may be related to increased bone resorption in these lesions. In addition, osteoblastic involvement was seen in FD and OS. Note: The superscript + is where it appears. Programs to copy some formatting errors. / O sistema RANK (receptor activator of nuclear factor Kappa-Beta)-RANKL (receptor activator of nuclear factor-kappa beta ligand)-OPG (osteoprotegerin) constitui uma das principais vias de diferenciação e ativação dos osteoclastos e alterações nessa via tem sido associadas a diversas lesões relacionadas ao osso (LRO), benignas e maligna como no osteossarcoma (OS). Esse sistema quando desregulado induz reabsorção, e no caso das LROs, através da substituição do tecido ósseo por um tecido fibroso com a presença de várias formas de ossificação. E nesse contexto outra proteína, a osteocalcina (OC), que é um marcador tardio de ossificação, desempenha um papel fundamental no diagnóstico destas lesões. Portanto, o objetivo do presente estudo foi identificar, quantificar e comparar células RANK+, RANKL+, OPG+ e OC+ em lesões dos maxilares com envolvimento ósseo: fibroma ossificante (FO), displasia fibrosa (DF), cisto ósseo simples (COS), lesão central de células gigantes (LCCG) e osteossarcoma (OS). As células RANK+, RANKL+, OPG+ e OC+ foram identificadas pela técnica da imunoistoquímica, método da imunoperoxidase e do polímero, em 10 amostras de FO, DF, COS, LCCG e 5 amostras de OS. Quando comparado as lesões entre si, tanto nas células fibroblásticas estromais quanto da matriz óssea, nossos resultados demonstraram que os ativadores da reabsorção óssea (RANK/RANKL) apresentam uma maior expressão no FO e LCCG e, o inibidor da reabsorção (OPG) e a OC apresentaram maior na DF e COS. Em adição, nossos achados revelam que o OS apresenta alta expressão de todas as proteínas avaliadas, quando comparadas àquelas das LROs. Todavia, uma maior expressão de RANKL em relação à OPG e OC foi evidenciada nesta neoplasia. Nossos resultados sugerem que o FO, a LCCG e o OS expressam reguladores do metabolismo ósseo que podem estar relacionados com a reabsorção óssea aumentada nessas lesões, sendo que na DF e no OS foi observado envolvimento osteoblástico. OBS: A + está sobrescrita onde aparece. Programas copiam com erros certas formatações.

La mise en évidence du caractère actif de la phase de la résolution de l'inflammation a ouvert la porte à de nouveaux paradigmes thérapeutiques pour les maladies inflammatoires. Des paradigmes qui reposent sur l’utilisation de médiateurs actifs ayant le potentiel de promouvoir la résolution de l’inflammation. En d’autres termes, ces médiateurs régulent la réaction inflammatoire, initient la réparation tissulaire et conduisent au retour de l’homéostasie. Parmi ces médiateurs, la résolvine D1 (RvD1) présente des propriétés anti-inflammatoires et prorésolutives remarquables et ce, dans divers fonctions et tissus de l’organisme. Bien que les effets de la RvD1 aient été bien caractérisés par de nombreuses recherches, son rôle potentiel au niveau ostéoarticulaire demeure peu documenté. Dans cette étude, nous approfondissons les connaissances sur l’effet de la RvD1 dans la protection et la préservation de l’intégrité ostéoarticulaire, en étudiant sa capacité à réguler les principaux facteurs impliqués dans la physiopathologie articulaire. Dans un premier temps, nous avons démontré que la RvD1 est bien présente dans l’environnement articulaire et que ses niveaux sont plus élevés dans le liquide synovial des genoux arthrosiques par rapport aux genoux sains. Ces genoux sont obtenus d’un modèle d’arthrose chez le chien réalisé lors d’une étude antérieure. Par la suite, nous avons étudié ses effets sur les composantes cellulaires de l’articulation. Sur les chondrocytes arthrosiques humains, nous avons démontré que la RvD1 inhibe l’expression des médiateurs inflammatoires et cataboliques induits par l'IL-1β, à savoir la COX-2, la PGE2, l’iNOS, le NO et la MMP-13. L’étude des voies de signalisation a ensuite révélé que la RvD1 s’oppose à l'activation de NF-κB / p65, p38 / MAPK et JNK1 / 2, induite par l’IL-1β. En plus de ces remarquables effets, la RvD1 confère une protection contre l’apoptose cellulaire et le stress oxydatif induits par le HNE, tel que démontré par l'inactivation des caspases, l'inhibition de la libération de la LDH, l’augmentation des taux de la Bcl-2 et de l’AKT, ainsi que la stimulation du GSH. À côté des chondrocytes, la RvD1 a montré des effets puissants sur les ostéoclastes. En effet, elle inhibe la différenciation et l'activation des ostéoclastes tel que démontré par l’inhibition de l’expression de TRAP et de la cathepsine K. Elle réduit l’expression de TNF-α, de l’IL-1β, de l’IFN-γ, de la PGE2 et de RANKL, induite par le LPS et augmente celle de l’IL- 10. De plus, elle protège contre la résorption de la matrice d’hydroxyapatite ainsi que l’érosion ii de la matrice osseuse ex vivo, induites par le RANKL et le M-CSF. Enfin, l’étude des propriétés de la RvD1 dans un modèle d’arthrite chez la souris a révélé qu’elle réduit le score clinique, l'inflammation de la patte et la destruction des os et des articulations. De surcroit, elle inhibe les médiateurs inflammatoires et diminue significativement les marqueurs sériques du remodelage osseux et cartilagineux. Nos résultats sont très prometteurs et confirment le potentiel de la RvD1 dans la résolution de l’inflammation et le maintien de l’intégrité articulaires. Ils mettent ainsi en évidence sa pertinence clinique en tant qu’agent actif dans la prise en charge thérapeutique des maladies ostéoarticulaires. / The recognition of the proactive character of the resolution phase of inflammation has revealed alternative therapeutic paradigms for inflammatory conditions, based on the use of active mediators capable of promoting the resolution of inflammation. In other words, these mediators regulate the inflammatory response, initiate tissue repair and promote the return to homeostasis. Among them, resolvin D1 (RvD1) has remarkable anti-inflammatory and proresolutive properties. Although the effects of RvD1 have been well studied, its potential role in the osteoarticular tissues remains poorly documented. In this study, we expand our understanding of the potential of RvD1 in protecting and preserving joint integrity by studying its ability to regulate the major factors involved in the articular pathophysiology. First, we demonstrated that RvD1 is produced in the articular environment and that its levels are higher in the synovial fluid of osteoarthritic knees compared to healthy knees. The knees were obtained from an osteoarthritic dog model performed in a previous study. Therefore, we studied RvD1 actions on the cellular components of the joint. In human osteoarthritic chondrocytes, we demonstrated that RvD1 inhibits IL-1β-induced inflammatory and catabolic mediators, namely COX-2, PGE2, iNOS, NO, and MMP-13. This led to the study of signaling pathways, which revealed that RvD1 counter-regulates IL-1β-induced activation of NF-κB / p65, p38 / MAPK and JNK1 / 2. In addition, RvD1 confers a protection against cellular apoptosis and oxidative stress induced by HNE, as revealed by caspases inactivation, LDH inhibition, as well as increased levels of Bcl-2, AKT, and GSH. In addition to chondrocytes, RvD1 showed remarkable effects on osteoclasts. Indeed, it inhibits osteoclast differentiation and activation, as demonstrated by the inhibition of TRAP and cathepsin K expression. Moreover, it reduces LPSinduced TNF-α, IL-1β, IFN-γ, PGE2 as well as RANKL and concurrently increases IL-10 expression. Furthermore, it inhibits RANKL and M-CSF-induced hydroxyapatite matrix degradation and bone matrix erosion, ex vivo. Finally, the study of the properties of RvD1 in a mouse model of arthritis, revealed that it alleviates the clinical score, paw inflammation, as well as bone and joint destruction. Furthermore, it reduces the inflammatory mediators and significantly decreases serum markers of bone and cartilage remodeling. Our results are very promising and confirm the high potential of RvD1 in resolving inflammation and preserving joint integrity. They highlight its clinical relevance as a therapeutic agent for the management of osteoarticular diseases.

In addition to classical adhesion structures like filopodia or focal adhesions, dendritic cells similar to macrophages and osteoclasts assemble highly dynamic F-actin structures called podosomes. They are involved in cellular processes such as extracellular matrix degradation, bone resorption by osteoclasts, and trans-cellular diapedesis of lymphocytes. Besides adhesion and migration, podosomes enable dendritic cells to degrade connective tissue by matrix metalloproteinases. SWAP-70 interacts with RhoGTPases and F-actin and regulates migration of dendritic cells. SWAP-70 deficient osteoclasts are impaired in F-actin-ring formation and bone resorption. In the present study, we demonstrate that SWAP-70 is not required for podosome formation and F-actin turnover in dendritic cells. Furthermore, we found that toll-like receptor 4 ligand induced podosome disassembly and podosome-mediated matrix degradation is not affected by SWAP-70 in dendritic cells. Thus, podosome formation and function in dendritic cells is independent of SWAP-70.

Chaque année, des chevaux de course décèdent de fractures complètes lors d’entrainement ou de course. A l’exercice, les charges supra-physiologiques cycliques entrainent des microfissures indiscernables par les techniques d’imagerie in vivo actuelles. Les ostéoclastes recrutés aux sites lésés induisent localement une lyse osseuse et une ostéopénie par résorption excessive, créant une concentration de contrainte à l’origine de fracture complète. Cependant, le rôle biologique des ostéoclastes dans les fractures de stress n’est à ce jour pas clairement identifié. Les objectifs de cette étude ont été d’établir des cultures in vitro d’ostéoclastes équins, corréler le nombre d’ostéoclastes avec l’isoforme 5b de l’enzyme phosphatase acide tartrate-résistante (TRACP 5b), corréler la résorption osseuse avec la TRACP-5b et le télopeptide C-terminal du collagène de type I (CTX-I) et étudier les effets de facteurs d’inflammation sur l’activité ostéoclastique. Après aspiration de moelle osseuse sternale, les cellules souches hématopoïétiques ont été isolées, conservées dans une banque cellulaire, décongelées, différenciées en ostéoclastes, avec ou sans os équin, et stimulées par des facteurs inflammatoires (IL-1β ou LPS). CTX-I et TRACP-5b ont été dosés par ELISA. Le nombre d’ostéoclastes colorés à la phosphatase acide tartrate-résistante et les aires de résorption osseuse colorées au bleu de toluidine ont été évalués. Dans les cultures d’ostéoclastes, la TRACP-5b augmentait (p < 0,0001) avec le temps et était corrélée (r = 0,63, p < 0.001) avec le nombre d’ostéoclastes. Dans les cultures d’ostéoclastes sur os, le CTX-I (p = 0,0018) et la TRACP-5b (p = 0,02) augmentaient avec le temps, étaient corrélés ensemble (r = 0,64, p < 0,002) et étaient tous deux corrélés avec la résorption osseuse (respectivement, r = 0,85, p < 0,001 et r = 0,82, p < 0,001). La stimulation inflammatoire n’a eu aucun effet significatif. Ostéoclastes équins et résorption osseuse ont été obtenus avec succès sur os équin à partir d’aspiration de moelle osseuse sternale. Pour la première fois, CTX-I et TRACP-5b ont été mesurés dans des cultures d’ostéoclastes équins. In vitro, CTX-I est un biomarqueur de résorption osseuse équine et TRACP-5b un biomarqueur du nombre d’ostéoclastes et de résorption osseuse équins. Des recherches ultérieures sont nécessaires afin d’évaluer si la TRACP 5b sérique permet la détection de toute résorption osseuse excessive chez les chevaux de course. / Every year racehorses die from complete catastrophic fractures in training and racing. Supra-physiological cyclic loads during exercise cause bone microcracks not discernible with current imaging in vivo. Osteoclasts recruited to the sites of the damage induce focal bone lysis and osteopenia by excessive resorption, creating a stress riser area susceptible to complete fracture. However, the biological impact of osteoclasts in stress fractures is not entirely understood. Our objectives were to establish in vitro cultures of equine osteoclasts, to correlate osteoclast numbers with the tartrate-resistant acid phosphatase 5b isoform (TRACP-5b), to correlate bone resorption with the TRACP-5b and the C-terminal telopeptide of type I collagen (CTX-I), as well as to investigate the effects of inflammatory factors on osteoclast activity. Following equine sternal bone marrow aspirations, hematopoietic stem cells were isolated, stored in a cell bank, thawed, differentiated into osteoclasts, with or without equine bone slices, and they finally underwent inflammatory stimulation (IL-1β or LPS). CTX-I and TRACP 5b were assayed by ELISAs. Osteoclasts stained with tartrate resistant acid phosphatase were counted and bone resorption areas stained with toluidine blue were measured. In the osteoclast cultures, the TRACP 5b increased (p < 0.0001) with time and correlated (r = 0.63, p < 0.001) with osteoclast number. In the osteoclast-bone cultures, both CTX-I (p = 0.0018) and TRACP-5b (p = 0.02) increased with time, correlated with each other (r = 0.64, p < 0.002) and both correlated with bone resorption (r = 0.85, p < 0.001 and r = 0.82, p < 0.001, respectively). The inflammatory stimuli had no significant effects. Equine osteoclasts and bone resorption were successfully induced on equine bone from sternal bone marrow aspiration. For the first time CTX-I and TRACP-5b were measured in equine osteoclast cultures. In vitro, CTX-I is a biomarker of equine bone resorption and TRACP-5b a biomarker of equine osteoclast number and bone resorption. Further investigations are required to measure the serum TRACP-5b capacity to detect excessive skeletal resorption in racehorses.

Made available in DSpace on 2014-12-17T15:32:29Z (GMT). No. of bitstreams: 1 KaruzaMAP_Tese.pdf: 829792 bytes, checksum: 60cd145c0f060b54f7dfbb5463648200 (MD5) Previous issue date: 2010-02-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The Giant Cell Lesions, both the Central Giant Cells Lesions (CGCL) as the Peripheral Giant Cells Lesions (PGCL), correspond to a group of oral lesions that are histologically similar entities; however they show a variable clinical behaviour. The purpose of this study was to compare the immunohistochemical expression of bone resorption factors RANK (Receptor Activator of Nuclear Factor kappa B), RANKL (Receptor Activator of Nuclear Factor kappa B Ligand) and OPG (Osteoprotegerin) between CGCL and PGCL. Additionally, these bone resorption factors were examined in terms of aggressiveness of these lesions. The sample consisted of 61 cases, 30 cases of PGCL and 31 CGCL (16 non-aggressive and 15 aggressive). The analysis was performed by quantification of mononuclear cells (MO) and giant multinucleated cells (CG) immunopositive to anti-RANK, anti-RANKL and anti-OPG antibodies in 10 fields. Moreover, according to the proportion between the amount of cells positive for RANKL and OPG, the cases were categorized into: RANKL>OPG, OPG>RANKL e RANKL=OPG. CGCL showed a higher amount of MO (p=0.002) and total cells (p=0.003) both positives to RANKL compared with the PGCL. Additionally, the CGCL revealed a significant association with the ratio of RANKL>OPG (p=0.001). Analysis of the bone resorption factors revealed no significant differences between aggressive and non-aggressive CGCL (p>0.05). It was observed a positive correlation between the markers themselves, and a negative correlation between lesion size and quantity of OPG positive MO cells (p=0,004) and total cells (p=0,009). Through these results, we suggest that the greatest CGCL resorptive potential compared to the PGCL, may have occurred to the high expression of RANKL. Furthermore differences in the biological behavior of aggressive and non-aggressive CGCL appear to be related to the expression of these bone resorption factors / As Les?es de C?lulas Gigantes, tanto as Les?es Centrais (LCCG) quanto as Perif?ricas (LPCG), correspondem a um grupo de les?es orais que apresentam-se histologicamente semelhantes, por?m demonstram um comportamento cl?nico vari?vel. O prop?sito deste estudo foi comparar a express?o imuno-histoqu?mica dos fatores de reabsor??o ?ssea RANK (Receptor Ativador do Fator Nuclear kappa B), RANKL (Ligante do Receptor Ativador do Fator Nuclear kappa B) e OPG (Osteoprotegerina) entre LCCG e LPCG. Adicionalmente, esses fatores foram analisados nas LCCG quanto ? agressividade destas. A amostra consistiu de 61 casos, sendo 30 casos de LPCG e 31 de LCCG (16 n?o-agressivos e 15 agressivos). A an?lise foi realizada por meio da quantifica??o das c?lulas mononucleadas (MO) e c?lulas gigantes multinucleadas (CG) imunopositivas aos anticorpos anti-RANK, anti-RANKL e anti-OPG, em 10 campos. Al?m disso, de acordo com a propor??o entre quantidade total de c?lulas positivas para RANKL e para OPG, os casos foram categorizados em: RANKL>OPG, OPG>RANKL e RANKL=OPG. As LCCG apresentaram maior quantidade de MO (p=0,002) e c?lulas totais (p=0,003) positivas para RANKL, em compara??o com as LPCG. As LCCG ainda revelaram uma associa??o significativa com a propor??o de RANKL>OPG (p=0,001). A an?lise dos fatores de reabsor??o ?ssea n?o revelou diferen?as significativas entre LCCG agressivas e n?o-agressivas (p>0,05). Foi constatada correla??o positiva dos marcadores entre si, bem como uma correla??o negativa entre o tamanho das les?es e a quantidade de MO (p=0,004) e c?lulas totais (p=0,009) positivas para OPG. Diante desses resultados, concluise que o maior potencial reabsortivo das LCCG frente ?s LPCG pode ser decorrente da elevada express?o de RANKL. Al?m disso, as diferen?as nos comportamentos biol?gicos de LCCG agressivas e n?o-agressivas parecem n?o estar relacionadas com a express?o desses fatores de reabsor??o ?ssea.

Indiana University-Purdue University Indianapolis (IUPUI) / Signal Transducer and Activator of Transcription 3 (STAT3) is known to be related to bone metabolism. Mutation of STAT3 causes a rare disorder in which serum levels of IgE are elevated. This causes various skeletal problems similar to osteoporosis. To examine the effect of STAT3 in the osteoclast, we obtained two osteoclast specific STAT3 knockout mouse models: one using the CTSK promoter to drive Cre recombinase and another using a TRAP promoter. Examination of these mice at 8 weeks of age revealed a decreased trabecular bone volume in CTSK specific STAT3 knockout mice along with a slight decrease in osteoclast number in both CTSK and TRAP specific STAT3 knockout females. We also noticed changes in bone mineral density and bone mechanical strength in females. These data suggest that STAT3 plays a part in the function of the osteoclast.